PROJECT SUMMARY ? OVERALL This P20 application seeks to establish the Exploratory Vanderbilt Alzheimer?s Disease Research Center (VADRC) at Vanderbilt University Medical Center and Vanderbilt University in Nashville, Tennessee. The VADRC will leverage and build upon the foundational elements of the Vanderbilt Memory and Alzheimer?s Center created in 2012, including established outreach and recruitment pipelines as well as clinical, neuroimaging, genetic, and biospecimen data collection, processing, storage, and dissemination protocols. Simultaneously, the VADRC will establish essential infrastructure appropriate for a future P30 Alzheimer?s Disease Research Center with a focus on identifying molecular factors that increase Alzheimer?s disease risk or promote resilience. The VADRC mission will be to enhance knowledge to solve the complexities underlying the pathophysiology, early identification, and treatment of Alzheimer?s disease and related dementias. Our mission and goals align with the 2011 National Alzheimer?s Project Act. During the P20 award, we will establish Administrative, Clinical, and Biomarker Cores that work in harmony to facilitate and enhance innovative basic, translational, and clinical science in Alzheimer?s disease and related dementia across Vanderbilt?s campus. This effort will leverage rich precision medicine techniques and tools available at Vanderbilt and innovative pathways to identify novel therapeutics while supporting faculty recruitment and retention, integrated team science, and mentorship at all levels. The P20 mechanism will provide essential research resources and foster a strong intellectual community to support existing studies and enable new opportunities for transformative research. Within the Clinical Core, we will complete comprehensive clinical, cognitive, neuroimaging, genetic and biospecimen assessment on a newly established research cohort of aging adults ranging from cognitively unimpaired to mild Alzheimer?s disease, including neuropathological analyses as participants come to autopsy. Cross-Core and interdisciplinary collaborations throughout campus and with national repositories (including the National Alzheimer?s Coordinating Center) will support data collection, sharing, and dissemination. The VADRC will also enhance clinical relationships, community partnerships, and educational opportunities to promote awareness, increase research participation, and provide an interdisciplinary training environment. The Center will serve as the institutional hub of all research and educational opportunities in Alzheimer?s disease. Simultaneously, the VADRC will contribute to national efforts to advance Alzheimer?s disease research, clinical care, and educational activities by establishing relationships with other Alzheimer?s Disease Research Centers, contributing to national initiatives, and enhancing collaborations to maximize contributions to the field. The Center will be the first of its kind in the region and would help to serve the growing population of Tennesseans and southern Americans suffering from Alzheimer?s disease and related dementias.